1. Field of the Invention
This invention relates to a class of virucidal compositions highly efficacious against common respiratory viruses such as rhinoviruses, parainfluenza viruses, and adenoviruses and the methods and products utilizing such compositions. In particular, the invention relates to a novel type of virucidal composition which can be applied to a variety of substrates or carriers such as cellulosic webs, nonwoven structures, and textile-based materials. In addition, the class of virucidal compositions comprising this invention may also be incorporated into nasal sprays, facial creams, hand lotions, lipsticks, and similar cosmetic preparations. The compositions may also be used as ingredients in kitchen and bathroom cleansers, furniture and floor polishes, and similar household preparations. Along these same lines, the compositions can be used in hand-washing soaps, soapy lotions, and "wet" wipe type products, e.g., products of the type shown in U.S. Pat. Nos. 3,057,467, 3,836,044 and 4,017,002. In addition to their virucidal activity, the compositions of the invention have general germicidal activity, that is, in addition to viruses, the compositions also kill bacteria and yeasts.
Virologists knowledgeable in the field of respiratory viruses generally agree that rhinoviruses, influenza viruses, and adenoviruses are among the most important group of pathogenic agents which cause respiratory illnesses. Rhinoviruses, in particular, are thought to be the principle causative agent of what is generally known as "the common cold".
Rhinovirus, which causes cold symptoms, belongs to the picornavirus family. This family lacks an outer envelope, and therefore, is characterized as "naked viruses". Although more than 100 different antigenic types of rhinoviruses are known, they share certain centrally important attributes. For instance, all are acid labile, and all contain single-stranded RNA (ca. 2.6.times.10.sup.6 daltons). All are difficult to inactivate by common germicides such as quaternary ammonium compounds.
Adenoviruses include more than thirty antigenic types. When they invade the respiratory tract, they cause inflammation of the tissues leading to symptoms of pharyngitis, bronchitis, etc. While most adenovirus infections occur in childhood, infections of adults are far from uncommon. Like rhinoviruses, adenoviruses lack an envelope, (i.e. naked) but the adeno-nucleus, in contrast to the rhino-nucleus, contains a double-stranded DNA, and is not characterized as acid labile. Adenoviruses are unusually resistant to inactivation.
Parainfluenza viruses, which belong to the paramyxovirus family, play an important role in the occurrence of lower respiratory diseases in children and upper respiratory diseases in adults. The parainfluenza viruses are RNA-containing viruses endowed with an ether-sensitive, lipoprotein envelope surrounding the nucleocapsid. These viruses are resistant to inactivation by carboxylic acids in low concentrations.
Recent work by Dick and others (Dick, E. C. and Chesney, P. J., "Textbook of Pediatric Diseases", Feigin, R. D. and Cherry, J. D. ed., Vol. II, p. 1167 (1981) W. B. Saunders Pub. Co., Phila., PA) has thrown considerable light on the mode of transmission of respiratory diseases caused by rhinoviruses. Although the exact mode of transmission of respiratory diseases is not fully understood, field studies by the above investigators have provided persuasive evidence that effective transmission of diseases such as common colds usually requires close association or contact--direct or indirect--between the infected subject and the potential victim. (Indirect contact may be looked upon as contact occurring via an intervening surface, e.g., table top, door knob, etc.). Thus, it may be possible to interrupt the chain of infection and reduce its potential to spread if the viruses can be rendered ineffective as they emerge from an infected person's nose or mouth by immediate exposure to a virucidal agent. Moreover, after emergence, viruses which may ensconce themselves on the infected person's face or hands may also be "killed" if a suitable virucidal agent is quickly brought into contact with the appropriate anatomical surface, i.e., face, hands, etc. A facial tissue, containing a fast-acting, efficacious virucidal composition would offer a simple means of accomplishing the tasks mentioned above.
A long-felt need has existed for a safe and inexpensive virucidal agent effective against common respiratory viruses. Simple household germicides are not effective against rhino- and adenoviruses.
2. Description of the Prior Art
U.S. Pat. No. 4,045,364 to Richter discloses a disposable paper impregnated with an iodophor (i.e. iodine and a carrier) having germicidal properties and useful as a pre-wash in a surgical scrub routine. The patentee discloses that the stability of the iodophor is enhanced at a lower pH and that small quantities of weak organic acids such as citric acid or acetic acid can be added to achieve pH control. U.S. Pat. No. 3,881,210 to Drach et al. describes a pre-moistened wiper for sanitary purposes which can include a bactericide. U.S. Pat. No. 3,654,165 to Bryant et al. discloses a cleaner/sanitizer for wiping purposes including iodine providing bactericidal action. U.S. Pat. No. 3,567,118 to Shepherd et al. discloses a fibrous material for cleaning purposes having a coating of a hydrophilic acrylate or methacrylate containing, inter alia, a bactericide. German product brochure entitled "Sagrosept.RTM. Cloths", Schulke and Mayr GmbH, Robert-Koch-Str. 2, 2000 Norderstedt, West Germany, describes wet disinfection and cleaning cloths containing 2-propanol, 1-propanol, benzoic acid and lactic acid as active ingredients. See also German Patent No. 1,924,490.
While the prior art has disclosed that iodine compositions and products have a wide-spectrum virucidal effect, there has yet to be developed commercially an inexpensive product that successfully interrupts the spread of viruses such as rhinovirus or influenza virus. Problems with iodine result, for example, from its toxicity, and the fact that it is an irritant for animal tissue. The action of iodine is non-selective as between bacterial and mammalian protein, and its uncontrolled use upon the skin may cause severe irritation. Further, its activity may be diminished or neutralized by the action of biological fluids such as blood serum. Efforts to modify iodine to avoid these difficulties have not been completely successful.
References exist in the literature on the bactericidal action of acids such as citric, (e.g., Reid, James D., "The Disinfectant Action of Certain Organic Acids", American Journal of Hygiene, 16, 540-556 (1932)). However, virucidal action is fundamentally different from bactericidal action in that viruses and bacteria represent different microorganisms with different characteristics. For instance, viruses do not replicate outside host cells whereas bacteria do. Quaternary ammonium compounds such as benzalkonium chloride are often effective against bacteria but not against viruses such as the various rhinoviruses.
Although it is known that rhinoviruses are labile to aqueous solutions of acids under low-pH conditions (e.g. Davis, B. D. et al; "Microbiology" p. 1303. Harper E. Row (Publishers) New York, 1973 and Rueckert, R. R., "Picornaviral Architecture" Comparative Virology - Academic Press New York (1971), pp. 194-306), known references do not mention the utilization of this concept in epidemiological contexts such as interruption of the chain of infection caused by rhinoviruses. To the best of our present knowledge the only systematic study of the virucidal action of organic acids (citric, malic, etc.) which exists in the generally available literature, was carried out by Poli, Biondi, Uberti, Ponti, Balsari, and Cantoni (Poli, G. et al: "Virucidal Activity of Organic Acids" Food Chem. (England) 4(4)251-8 (1979)). These workers found that citric, malic, pyruvic and succinic acids, among others, were effective against herpesvirus, orthomyxovirus and rhabdovirus (Rabies virus). Their experiments were carried out at room temperature with aqueous solutions of pure acids. No substrate or carrier was used. The three viruses chosen for study by these workers were all "enveloped" viruses, resembling, in that regard, parainfluenza 3. Poli et al also observed that these acids were not effective against adenovirus which, it will be recalled, is a "naked" virus. Based on this, they concluded that these acids were effective against "enveloped" viruses but not against "naked" viruses.
It is known to those skilled in the art that adenoviruses are resistant to acids.
Archiv fur Libensmittelhygiene, 29, 81-120 (1978) reports a strain of adenoviruses to be susceptible to certain disinfectant surface active agents in aqueous solution. There is no suggestion, however, of combining such disinfectant surface active agents with an organic acid or with a substrate or carrier.
The use of acidic solutions of anionic surfactants as sanitizers in the dairy, beverage and food processing industries is discussed in Dychdala, G. R., "Surface-Active Agents: Acid-Anionic Compounds", Disinfection, Sterilization, and Preservation, S. Block (ed.), 3rd edition, pages 330-333 (1983). Significantly, this reference specifically teaches that such sanitizers must be used with care and kept out of the reach of children because of their acidity. See also U.S. Pat. No. 3,969,258 and German Offenlegungsschrift No. 2,539,016. In addition, see U.S. Pat. Nos. 4,105,782 and 4,105,783 which teach that to be nonirritating, products such as shampoos, lotions, and creams should have pHs in the range of 3.5 to 7.5.
The use of anionic surfactants as bactericides is discussed in Baker et al., "The Bactericidal Action of Synthetic Detergents", Journal of Experimental Medicine,Vol. 74, pages 611-620 (1941); Cowles, P. B., "Alkyl Sulfates: Their Selective Bacteriostatic Action", Yale Journal of Biology and Medicine, Vol. 11, pages 33-38 (1938); and Newton, B. A., "Surface-Active Bactericides", Symposium for the Society for General Microbiology, No. 8, pages 62-93 (1958). The Baker et al. and Cowles references report that under the experimental conditions employed, anionic surfactants were found to be ineffective against Gram-negative organisms. The Newton reference (at page 67) points out that various substances, including soaps, can prevent anionic and cationic surfactants from killing bacteria. Similarly, U.S. Pat. No. 3,244,636 reports interference between detergent compositions and antimicrobial agents such that the detergent and the antimicrobial agent are each less effective when used in the presence of each other.
U.S. Pat. No. 3,650,964 discloses low foaming sanitizer compositions employing selected anionic surfactants in an acid medium. U.S. Pat. No. 3,141,821 discloses allegedly synergistic combinations of a bacteriostatic compound, such as hexachlorophene, and an acid solution of an anionic surfactant. The patent describes formulating the compositions in a pre-surgical scrub, an acn preparation, an after-shave lotion, an under-arm deodorant, a body powder, and a detergent bar. See also German Auslegeschrift No. 1,105,549 and German Offenlegungsschrift No. 2,312,280.
U.S. Pat. No. 3,408,298 to Baravalle discloses germicidal compositions which include a quaternary ammonium complex in combination with nonionic, cationic, or anionic detergents. These compositions are said to be suitable for use in preparations which come into contact with skin. Similarly, U.S. Pat. No. 3,023,144 describes a fungicide/bactericide made from d-limonene and salicylic acid which can be topically applied, and U.S. Pat. No. 3,278,370 describes soaps which include higher alkyl benzoates, such as sodium dodecylbenzoate, as bacteriostatic agents.